The objectives of the proposed research are to develop simplified, inexpensive detectors for high performance liquid chromatography (HPLC) and super-critical fluid chromatography (SFC) and to demonstrate the utility of these new detectors for solution of significant biomedical problems. Specific objectives include extension of the successful "Thermospray" approach to lower mass flows such as are involved in capillary and microbore LC and in SFC, coupled with additional basic studies of the processes involved in thermospray. The latter studies are aimed at achieving improved performance over the entire range of useful flow rates ranging from submicroliter/min for capillary LC to the mL/min flows used in conventional packed column LC. Emphasis will also be placed on improving the structural information available from LC-MS. Techniques proposed include conventional EI with thermospray vaporization, and a new technique for electron impact dissociation of ions formed directly by thermospray. These fundamental advances will be combined with simplified vacuum technology and improved automatic control of the integrated LC-MS system to provide simple, reliable mass selective detectors which are acceptable for use in the chromatography laboratory. The utility of this new instrumentation will be demonstrated by application to selected biomedical problems.